. Mycobacterium tuberculosis, the primary agent of tuberculosis, infects half of the world's population and is one of the most important diseases in the world from the standpoint of human morbidity and mortality. M. tuberculosis has also emerged as a highly prevalent opportunistic pathogen in AIDS patients. Moreover, multi-drug resistant tuberculosis has emerged as a major new and highly fatal threat to AIDS patients and others. A safe, effective vaccine against M. tuberculosis is sorely needed. The development of such a vaccine in the near future is the goal of the studies proposed in this application. Previous studies from this laboratory including studies completed under this grant have demonstrated the importance of extracellular proteins of M. tuberculosis in inducing both cell- mediated and protective immunity in the guinea pig model of pulmonary tuberculosis, a model noteworthy for its relevance to human tuberculosis. These studies demonstrated for the first time the feasibility of a subunit vaccine against tuberculosis. Current studies have extended these observations to purified extracellular proteins of M. tuberculosis, a critical step toward the development of a subunit vaccine because it will allow the development of a defined, consistent, fully characterized vaccine against tuberculosis. The goal of this project is to study systematically purified extracellular proteins of M. tuberculosis for their capacity to induce cell-mediated and protective immunity against tuberculosis in the guinea pig model.